PRESS RELEASE
SUMMARY OF THE WEBCAST HELD ON MARCH 4,
2024 PROVIDING AN UPDATE ON AB SCIENCE DEVELOPMENT
Paris, March 7, 2024, 3pm CET
AB Science SA (Euronext -
FR0010557264 - AB) is providing a summary of the live webcast held
on March 4, 2024, giving an update on AB Science development.
The webcast presentation is available on the
company’s website, in the section « Press
Releases »: https://www.ab-science.com/news-and-media/press-releases/
The presentation covered four topics:
-
Status of conditional approval application of masitinib in ALS with
EMA and Health Canada
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Status of the masitinib platform clinical development program
-
Status of masitinib licensing partnership
-
Status of the microtubulin platform clinical development
program
-
Status of masitinib and AB8939 intellectual property
Status of conditional approval
application of masitinib in ALS with EMA and Health
Canada
-
Regarding EMA, the application was filed in August 2022. An Oral
Explanation was planned in January 2024, however, CHMP proposed
that AB Science submit a written response to the List of
Outstanding Issues at D195 of the procedure, instead of addressing
these issues through the Oral Explanation, which is unusual. A
decision is now expected by the end of Q2 2024.
-
Regarding Health Canada, a Notice of Deficiency-Withdrawal (NOD/w)
has been issued and AB Science intends to submit a Request for
Reconsideration. This reconsideration process involves new
assessors and offers the possibility to have an opinion from a
panel of experts. A decision is now expected by the end of Q3/Q4
2024.
Of note, the press release dated 26 February
2024 incorrectly stated that Health Canada issued a Notice of Non
Compliance – Withdrawal (NON/w) when the decision issued was in
fact a Notice of Deficiency – Withdrawal (NOD-W).
The issuance of NOD-W or NON-W indicate
different regulatory decisions. A NOD-W is issued if, during the
scientific review of the response to a Notice of Deficiency (NOD),
it is found that the submission/application remains deficient. On
the other hand, a Notice of Non-Compliance Withdrawal is issued
when, during the scientific review of the response to a Notice of
Non-Compliance (NON), it is determined that the submission remains
non-compliant.
Three key major clinical objections and intended
counterarguments for reconsiderations have been presented. They are
the following:
-
Amendments
-
Multiple amendments have been made that create uncertainty on the
reliability of study data. Several concerns were resolved, namely,
changing study status from phase 2 to phase 3, the fact that
multiple amendments may be an inevitability, that amendments were
not data-driven, that the study had broad inclusion criteria and
there may be a need to limit heterogeneity, and that post-onset
decline of 1.1 point per month may be relevant.
-
However, Health Canada was concerned that amendments were late and
not sufficiently justified. AB Science intends to justify that the
distinction between Normal and Fast progressors was made when the
data were entirely blinded and in a sufficiently prospective manner
since 88% of the data still needed to be acquired at that time, and
that the amendment was justified to minimize expected high missing
data due to discontinuations from Fast progressors (confirmed to be
>50% at week 48).
-
Missing data
-
The concern regarding non-linearity of the ALSFRS-R data set
distribution used for primary analysis (ANCOVA test) was
resolved.
-
However, Health Canada was concerned that the treatment of missing
data using LOCF methodology could potentially create a bias in
favor of treatment.
-
AB Science intends to justify that sensitivity analysis of the
primary analysis based on non LOCF recognized methods are
successful and convergent (multiple imputational model, jump to
reference, copy incremental model), and that the CAFS endpoint,
incorrectly assumed by the Agency to be based on LOCF methodology,
whereas it is not, approached the conventionally statistically
significant outcome of 5% (p=0.0776), even though the study was not
powered for this secondary endpoint.
-
Application of EMA guideline on subgroups
-
Health Canada was concerned that the new proposed claim in patients
with ALS prior to any complete loss of function is considered post
hoc and that overall survival benefit in this claim could have been
biased by confounding factors.
-
AB Science intends to justify that in the EMA guidance
(EMA/CHMP/539146/2013) on the investigation of subgroups in
confirmatory clinical trials, it is written that the guideline is
applicable to a subgroup that has not been pre-specified.
-
In this claim, the treatment effect is exceptionally strong based
on CAFS (p=0.029) and survival (+22 months p=0.0192). Furthermore,
OS is the gold standard endpoint in ALS and is unbiased regardless
of post study treatments because no drug has demonstrated OS
benefit (except riluzole, which was available to all patients) and
because all patients had the same possibility to benefit from
tracheostomy or permanent or non-permanent ventilation.
Based on the supporting arguments and
counterarguments outlined above, AB Science intends to submit a
Request for Reconsideration. Other points of concern identified by
the agency will also be responded to.
Status of the masitinib platform
clinical development program
Masitinib offers a late stage and diversified
platform of 8 indications, primarily centered around
neuro-degenerative diseases (namely, amyotrophic lateral sclerosis,
progressive form of multiple sclerosis, mild and moderate
Alzheimer’s disease) and mast cell diseases (indolent systemic
mastocytosis, mast cell activation syndrome), but also sickle cell
disease, metastatic castrate refractory prostate cancer eligible to
docetaxel, and COVID-19.
-
In amyotrophic lateral sclerosis (ALS), no drug has generated a
consensus based on definitive evidence of efficacy. Enrolment in
the phase 3 confirmatory masitinib study (AB19001), is slower than
that of the previous (AB10015) study, due to design features of the
phase 3 (run-in period of 3 months, patient eligibility restricted
to moderate ALS severity, exclusion of newly registered drugs and a
blinded extension period).
-
In multiple sclerosis (MS), there is no approved drugs for
non-active secondary progressive MS and only one for primary
progressive MS. Masitinib stands-out as the only non BTK inhibitor
in phase 3 clinical development. The confirmatory phase 3 masitinib
study (AB20009) is authorized by the FDA and key European countries
and initiation is expected in 2024.
-
In Alzheimer’s disease (AD), masitinib is positioned in mild and
moderate forms of Alzheimer’s disease, where no novel treatment has
been approved. New treatments have been approved in early
Alzheimer. The confirmatory phase 3 masitinib study (AB21004) is
authorized by FDA and key European countries with initiation
expected in 2024.
-
In indolent systemic mastocytosis (ISM), masitinib has a different
positioning from other KIT-816 inhibitors and its benefits are
optimal on different symptoms such as neurological symptoms,
depression but also pruritus and flush. The confirmatory phase 3
masitinib study (AB15003) is on-going and additionally, a phase 2
study (AB20006) is also ongoing in MCAS, another mast cell disease
not involving the KIT-816 mutation.
-
In sickle cell disease (SCD), there is an increasing interest with
several new drugs being in clinical development; however, unlike
masitinib, none target mast cells, which are involved in Vaso
Occlusive Crisis. A phase 1/2 study, financed by the RHU program
for a budget of 10M€, is planned, with an objective to identify
biomarkers of a mast cell signature and to assess the efficacy of
masitinib in the treatment of acute and chronic complications. AB
Science will be free to continue the development of masitinib in
SCD based on phase 2 data with biomarkers.
-
In metastatic castrate refractory prostate cancer (mCRPC) eligible
to docetaxel, there is no drug registered in combination with
docetaxel and there is an unmet medical need after failure to
hormonotherapy and eligible to docetaxel. A first phase 3 study of
masitinib in combination with docetaxel was positive. Submission of
a confirmatory phase 3 study is planned in 2024, following
scientific advice received from EMA and FDA, who both recommended
to demonstrate benefit on radiographic progression free survival
with no need to prove efficacy on overall survival.
-
In COVID-19, read-out of two phase 2 studies is expected in 2024,
the first evaluating masitinib anti-inflammatory activity in
hospitalized patients in need of oxygen with moderate and severe
COVID-19, and the second one evaluating masitinib anti-viral
activity in ambulatory or hospitalized patients with symptomatic
mild and moderate COVID-19 and with comorbidities.
Status of masitinib licensing
partnership
Discussions for masitinib licensing with a
pharmaceutical company are ongoing and the process is expected to
be completed by the end of 2024.
The scope of the license is mainly
neurodegenerative indications, including ALS.
The discussions are with companies that do not
condition the signature of a binding offer to a positive opinion
from EMA and Health Canada in ALS.
AB Science is currently aiming to develop a
liquid formulation for masitinib in ALS. A liquid formulation would
be beneficial for ALS patients because they have difficulties in
swallowing. A liquid formulation is beneficial for the masitinib
development plan as differential pricing will be facilitated
between ALS (liquid formulation) and other indications (tablets).
The development of any new formulation will require bioequivalence
studies and is expected to take two years.
Status of the microtubulin platform
clinical development program
The microtubule destabilizer agents (MDAs)
platform is focused in haemato-oncology with two drugs, AB8939 and
AB12319.
AB8939 has the potential to improve acute
myeloid leukemia (AML) treatment based on three differentiating
features of its mechanism of action.
-
AB8939 is not metabolized by an enzyme called myeloperoxidase,
produced by the disease itself, unlike other MDAs.
-
AB8939 avoids multidrug resistance because it does not bind and is
not transported by PgP/BRCP, so it is not washed out from the
cells, unlike other MDAs.
-
AB8939 has a strong synergistic effect with reference treatment
azacitidine, called Vidaza.
The phase 1 study of AB8939 has completed its
first step (determination of maximum tolerated dose following 3
consecutive days of AB8939 treatment), and key agencies have
authorized this study to proceed with the next step (determination
of maximum tolerated dose following 14 consecutive days of AB8939
treatment).
The phase 1 is expected to be completed in 2024
and a phase 2 will be initiated in 2025 with an intention to design
the study to support accelerated approval.
Status of masitinib and AB8939
intellectual property
Masitinib intellectual property rights are
protected until 2036 in mastocytosis, until 2037 in ALS, and
potentially until 2041 in MS and ALZ and 2042 in prostate
cancer.
AB8939 intellectual property rights in AML are
secured until 2036 through a ‘composition of matter’ patent and
potentially until 2044 in AML with chromosome abnormality (MECOM)
through a ‘second medical use’ patent.
About AB ScienceFounded in
2001, AB Science is a pharmaceutical company specializing in the
research, development and commercialization of protein kinase
inhibitors (PKIs), a class of targeted proteins whose action are
key in signaling pathways within cells. Our programs target only
diseases with high unmet medical needs, often lethal with short
term survival or rare or refractory to previous line of treatment.
AB Science has developed a proprietary portfolio of molecules and
the Company’s lead compound, masitinib, has already been registered
for veterinary medicine and is developed in human medicine in
oncology, neurological diseases, inflammatory diseases and viral
diseases. The company is headquartered in Paris, France, and listed
on Euronext Paris (ticker: AB).Further information is available on
AB Science’s website: www.ab-science.com.
Forward-looking Statements - AB
ScienceThis press release contains forward-looking
statements. These statements are not historical facts. These
statements include projections and estimates as well as the
assumptions on which they are based, statements based on projects,
objectives, intentions and expectations regarding financial
results, events, operations, future services, product development
and their potential or future performance.
These forward-looking statements can often be
identified by the words "expect", "anticipate", "believe",
"intend", "estimate" or "plan" as well as other similar terms.
While AB Science believes these forward-looking statements are
reasonable, investors are cautioned that these forward-looking
statements are subject to numerous risks and uncertainties that are
difficult to predict and generally beyond the control of AB Science
and which may imply that results and actual events significantly
differ from those expressed, induced or anticipated in the
forward-looking information and statements. These risks and
uncertainties include the uncertainties related to product
development of the Company which may not be successful or to the
marketing authorizations granted by competent authorities or, more
generally, any factors that may affect marketing capacity of the
products developed by AB Science, as well as those developed or
identified in the public documents published by AB Science. AB
Science disclaims any obligation or undertaking to update the
forward-looking information and statements, subject to the
applicable regulations, in particular articles 223-1 et seq. of the
AMF General Regulations.
For additional information, please contact:
AB ScienceFinancial
Communication & Media Relations investors@ab-science.com
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